Synthetic membranes and separating processes based on them have been known for a long time. In addition to classical applications, for example, seawater desalination using reverse osmosis or ultrafiltration of process water from electrophoretic dip painting to recover the paint, membrane processes are becoming increasingly important in the areas of food technology, medicine, and pharmacy. In the latter cases, membrane separating processes have the great advantage that the materials to be separated are not subjected to thermal stress or even damaged.
Often, an important prerequisite for the usability of membranes in these areas is the sterilizability of the membrane. For safety and ecological reasons at least, steam sterilization is preferred over chemical sterilization, for example, using ethylene oxide, or sterilization by radiation, especially by gamma radiation.
Steam sterilization normally involves a half-hour treatment of the membrane or membrane system with hot steam at temperatures in excess of 110.degree. C. Thus, the criterion of steam sterilizability severely limits the number of potential membrane materials. Thus, for example, membranes made of polyacrylonitrile are basically not steam-sterilizable because exceeding the glass temperature of the polymer results in an irreversible damage to the material and/or the membrane. In addition, hydrolysis-sensitive polymers, for example, certain polycarbonates and polyamides, cannot withstand hot steam sterilization unscathed.
Steam-sterilizable membranes made of polyether imides, polysulfones, or polyvinylidene fluoride are known, for example. A major disadvantage of these membranes consists in the hydrophobic nature of the membrane material, which prevents spontaneous wetting with aqueous media. Consequently, the membrane must be prevented from drying completely or the membrane must be treated with a hydrophobic agent, glycerin, for example, before drying.
Hydrophilic membranes are characterized by the fact that they are wettable with water. A measure of wettability is the wetting angle that a water drop forms with the surface of the membrane. In hydrophilic materials, this edge angle is always greater than 90.degree.. Phenomenologically, the wetting of a dialysis membrane can also be detected by the fact that a drop of water placed on the surface of the membrane penetrates the membrane after a short time.
Another serious disadvantage of hydrophobic materials consists in the fact that they often possess a powerful nonspecific adsorption capacity. Therefore, when hydrophobic membranes are used, frequently a rapid, closely adhering coating of the membrane surface with preferably higher-molecular-weight solution components takes place. This phenomenon, known as fouling, leads to a rapid deterioration of the membrane permeability. Subsequent treatment of the membrane with a hydrophilizing medium cannot prevent fouling in the long term.
Suggestions for hydrophilic membranes have already been proposed that do not suffer from these disadvantages. Thus, DE-OS 3,149,976 proposes using a polymer mixture for making a hydrophilic membrane that contains at least 15 wt. % polyvinylpyrrolidone in addition to polysulfone or polyamide. For hydrophilization of polyimide and polyether sulfone membranes, for example, EP-A-0,228,072 claims the use of polyethylene glycol in amounts from 44 to 70 wt. %, based on the polymer solution.
Hydrophilization of membranes by using large quantities of water-soluble polymers however has the disadvantage that the hydrophilic nature of the membrane constantly decreases when they are used in aqueous media, since the water-soluble polymer is washed out. This can create a situation such that the membrane material recovers its original hydrophobic nature and the negative accompanying phenomena associated with it and listed above are exhibited.
EP-A-0,261,734 describes the hydrophilization of polyetherimide membranes using polyvinylpyrrolidone. The polyvinylpyrrolidone is crossed linked in the non-swollen state to prevent the washing out effect. The membrane manufacturing process is very tedious and hence cost-intensive, since the solvent and precipitating agent must first be removed from the membrane after precipitation and prior to cross linking, but not the polyvinylpyrrolidone. It is only at this point that the cross linking of the polyvinylpyrrolidone is performed by using high temperature, radiation, or chemically using isocyanates, whose residues must be absolutely completely removed before the membrane is used in the food or medicine area.
The disadvantages described above can be avoided by using hydrophilic, yet water-insoluble, polymers for making the membranes. Thus, in a number of patents, for example, EP-A-0,182,506 and U.S. Pat. No. 3,855,122, the manufacture of membranes from sulfonated polymers is claimed. The methods described in these patents however are only suitable for making flat membranes. The membranes possess a high salt retention capacity and are used primarily for reverse osmosis.
Another approach to hydrophilic membranes is proposed in U.S. Pat. No. 4,207,182 and in two Japanese Disclosure documents (JP-OS 61-249,504 and JP-OS 62-49,912). According to these publications, hydrophilic membranes for ultrafiltration of aqueous solutions can be advantageously manufactured from mixtures of sulfonated and nonsulfonated polysulfone.
An important goal of the invention described in U.S. Pat. No. 4,207,182 is the use of highly concentrated polymer solutions to manufacture membranes which nevertheless are characterized by a high hydraulic permeability. This is accomplished by using polymer mixtures, with the percentage of sulfonated polysulfone based on the total polymer mixture of nonsulfonated and sulfonated polysulfone being between 10 and 30 wt. %.
A high hydraulic permeability however is not advantageous for all applications. Thus, high hydraulic permeability in dialysis results in reverse filtration and hence to contamination of the liquid to be dialyzed with undesired materials from the dialysate.
As indicated by the examples in U.S. Pat. No. 4,207,182, the membranes according to the invention are also characterized by high screening coefficients for dextran with a molecular weight of 110,000 daltons.
In view of the high hydraulic permeability and the associated high permeability for macromolecular substances with a molecular weight greater than 100,000 daltons, the membranes resulting from the claimed polymer mixtures are not suitable for hemodialysis. This is all the more so when one considers that the dialytic permeability of the membranes manufactured according to U.S. Pat. No. 4,207,182 is comparatively low.
U.S. Pat. No. 4,545,910 claims membranes that exhibit the performance data of a conventional ultrafiltration membrane. The material for the membrane can be chosen from a plurality of substances, including polyacrylonitrile compounds.
In manufacturing synthetic non-cellulosic membranes, such as those from materials such as polyethersulfone, polyamide, or polyacrylonitrile compounds, a number of properties of the material that play a role in the future application of the material must be taken into account.
Thus, such a membrane, if it is to be used for dialysis, must exhibit or produce histamine release which is as low as possible. Increased histamine release results in a series of unpleasant side effects in dialysis patients, such as headache and pain in the limbs as well as other pain states that have a negative effect on the health of the patient. The limiting value for histamine release of course must be determined individually for each person. This value depends on a plurality of factors (age, sex, weight, etc.) and therefore cannot be specified generally.
Histamine is a highly active biological substance so that in any event excessive release should be avoided. Reference is made in this connection, for example, to papers by E. Neugebauer et al., Behring Inst. Mitt., No. 68, 102-133 (1981) or W. Lorenz et al., Klin. Wochenschr. 60, 896-913 (1982).
A membrane of this kind should also exhibit values that are as low as possible for bradykinin generation. Bradykinin generation is likewise linked with unpleasant side effects that can pose a danger to dialysis patients (G. Bonner et al., J. of Cardiovasc. Pharm. 15 (Supplement 6), pp. 46-56 (1990). Even though the clinical significance of bradykinin generation like that of histamine release has not yet been completely studied, an attempt should be made to avoid whenever possible this generation which can be triggered by a high percentage of sulfonate compounds in the membrane through so-called "contact activation", during dialysis.